黄芪甲苷对Ⅰ型糖尿病大鼠心肌细胞PGC-1α和NRF-1表达的影响

摘要

Aim To investigate the effect of astragalo-side IV ( ASIV) on myocardial energy metabolism and mitochondrial biosynthesis in myocardial cells of dia-betic rats induced by streptozotocin ( STZ ) . Methods 50 SD rats at 6 weeks of age were assigned to 5 groups,10 for each group:control group, model group, ASIV 10 mg·kg-1 ·d-1 group, ASIV 20 mg·kg-1 ·d-1 group, ASIV 40 mg·kg-1 ·d-1 group. Except the control group,the remaining 40 were used to estab-lish type 1 diabetes model by the tail vein injection of STZ (35 mg·kg-1 ) . At the end of 16 weeks of treat-ment, left ventricular systolic pressure ( LVSP ) , left ventricular diastolic final pressure ( LVEDP ) and left ventricular maximum rising/falling rate ( ± dp/dtmax ) were tested. Pathological section was observed by HE staining. ATP, ADP, AMP levels were detected by ELISA. The expressions of PGC-1α and NRF-1 protein were assessed by Western blot. The expressions of PGC-1α and NRF-1 mRNA were determined by RT-PCR. Results Compared with control group, model group markedly elevated LVEDP and decreased LVSP, ± dp/dtmax , ATP/AMP and ATP/ADP ratio. Com-pared with model group, low-dose ASIV group did not change significantly,middle-dose ASIV group and high-dose ASIV group obviously decreased LVEDP, and im-proved LVSP, ± dp/dtmax , ATP/ADP and ATP/AMP ratio. Meanwhile, the expressions of PGC-1α and NRF-1 protein and mRNA were increased in a dose-de-pendent manner. Conclusion ASIV could promote mitochondrial biosynthesis, improve energy metabolism in myocardial cells of type 1 diabetic rats by PGC-1αand NRF-1 .%目的：探讨黄芪甲苷( ASIV)对链脲佐菌素( STZ)诱导的糖尿病大鼠心肌细胞能量代谢及线粒体合成的影响。方法50只6周龄的SD大鼠,分为5组,每组10只,分别是空白组、模型组、ASIV 10、20、40 mg·kg-1组。除空白组,其余40只尾静脉注射STZ(35 mg·kg-1)建立Ⅰ型糖尿病心肌病模型。连续给药16周后,检测其左心室收缩压( LVSP)、左心室舒张期末压( LVEDP )、左心室最大上升/下降速率(± dp/dtmax ),苏木精-伊红( HE)染色观察心肌病理切片。ELISA检测心肌组织中 ATP、ADP、AMP 的含量。 Western blot法检测心肌组织中过氧化体增殖物激活型受体γ共激活因子1α( PGC-1α)和核呼吸因子( NRF-1)蛋白表达, RT-PCR检测心肌组织中PGC-1α和NRF-1 mRNA的表达。结果与空白组相比,模型组大鼠的 LVEDP 上升, LVSP、± dp/dtmax下降, ATP/ADP、ATP/AMP比值均下降。与模型组相比,黄芪甲苷低剂量组变化不明显,中、高剂量组 LV-EDP下降,LVSP、± dp/dtmax上升, ATP/ADP、ATP/AMP比值均上升, PGC-1α与 NRF-1的蛋白表达和 mRNA 表达均增加,有一定的剂量依赖性。结论黄芪甲苷通过提高PGC-1α和NRF-1的表达促进Ⅰ型糖尿病大鼠心肌细胞内线粒体的生物合成,提高能量代谢。